Iris N. Mutiu, BS: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: The five-year survival rate for glioblastoma (GBM), grade 4 brain cancer, is less than 10%, and newly proposed intervention strategies have been minimally effective. High intake of plant-based foods has been associated with lower glioma risk, which introduces interest in elucidating their potential anticarcinogenic properties. Our objective was to characterize the chemical composition of 12 plant extracts and determine their efficacy and signaling effects on GBM cells.
Methods: We chose 12 plant-based foods across a variety of categories: vegetables (artichoke, spinach, broccoli), legumes (black and green lentils), grains (purple barley), fruits (aronia berry, apple), and herbs and spices (lavender, lemon balm, oregano, clove). Water extractions were performed, and the aqueous component underwent lyophilization after which total phenolics and subgroups were quantified. Extracts were sent for untargeted plant metabolomics to identify compounds and their relative quantification. Blood-brain barrier (BBB) penetrability of identified phenolics were assessed through calculating their multiparameter optimization (MPO) score, and their binding affinity to GBM-progression related proteins was estimated through computational docking. Human GBM cell lines (LN229, U87, LN18) were used to determine viability effects of the extracts. We further analyzed protein expression changes induced by potent extracts in vitro.
Results: Phenolic acids and unconjugated flavonoids in the extracts had high MPO scores ( >4.0) demonstrating potential for BBB penetrability. We discovered that total phenolics and flavonoids correlate with higher inhibition of GBM cells. Extracts that had the greatest lowering of cell viability were artichoke and lemon balm. In silico analysis shows flavonoid and phenolic acids have binding potential with angiopoietin-2 (ANG2) and its receptor, part of angiogenesis signaling. The artichoke treated cells showed significant decrease of ANG2 expression compared to untreated cells in the antibody array analysis.
Conclusions: Phenolic-rich plant extracts showed antineoplastic effects on GBM cells, and their polyphenols show potential to cross the BBB and inhibit progression-related proteins. This contribution is significant to understanding signaling effects of plant foods on GBM.
